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Purpose To describe clinical and molecular characteristics of Korean patients with aniridia and to compare the clinical phenotype between those having an identifiable PAX6 mutation and those not. Design Comparative case series. Participants A total of 14 Korean patients from 10 families with aniridia. Methods Complete ophthalmologic examinations were performed for all patients. PAX6 analysis included direct sequencing of all coding regions and multiplex ligation-dependent probe amplification (MLPA) to detect large deletions when the sequencing was negative. If the PAX6 analysis failed to reveal any identifiable mutations, genomic copy number variation analysis via array comparative genomic hybridization (CGH) and candidate gene PITX3 and FOXE3 sequencing were then performed. Main Outcome Measures Severity of ocular abnormalities and genetic findings. Results Sequencing of PAX6 exhibited 5 different heterozygous mutations in 8 patients from 5 families; 2 (p.Ser43Phe, IVS8-9C>G) were novel, and 3 (p.Arg208Trp, p.Arg317X, and p.X423L) have been previously reported. Among the remaining 6 patients in whom the PAX6 sequencing was negative, MLPA identified large deletions in 2 sporadic patients. However, the array CGH and candidate gene sequencing found no genomic or genetic abnormalities. The mutation detection rate was therefore 70%. Patients harboring an identifiable mutation in PAX6 had either a severe or a mild variant phenotype depending on the type of mutations. Likewise, among patients without an identifiable PAX6 mutation, their phenotypes varied widely from severe to very mild. Conclusions This study adds 2 novel PAX6 mutations to those previously reported, providing further evidence for genetic and phenotypic heterogeneity in aniridic ocular malformation. There was no difference in the clinical phenotype between patients with and without detectable mutations in the PAX6 gene. The wide variability of ocular phenotype regardless of the presence or absence of PAX6 mutations calls for a further appreciation of the complexity in the molecular diagnosis of aniridia and suggests that this ocular malformation may be better regarded as a group of heterogeneous disorders, rather than a single disease entity, associated with mutations in PAX6 and/or other genes located elsewhere in the human genome. Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Objective To present the technique and report the results of up to 36 months after allogenic central penetrating limbo-keratoplasty in conjunction with conjunctivoplasty, mitomycin C (MMC), and amniotic membrane (AM) transplantation in patients with bilateral limbal stem cell deficiency (LSCD). Design Retrospective, consecutive subject cohort study. Participants Case records of 20 eyes from 20 patients who presented with bilateral LSCD due to aniridia, chemical/thermal burn, cicatrizing pemphigoid, and chronic ocular surface inflammation and who were treated at the University Eye Hospital, Freiburg. Methods All eyes were treated with central limbo-keratoplasty in conjunction with conjunctivoplasty, MMC, and AM. There were 20 human leukocyte antigen-typed allolimbal transplants from cadaveric donors. All patients received systemic immunosuppression with mycophenolate mofetil or cyclosporine A. Main Outcome Measures Surgical success was measured by the duration for which a healthy corneal epithelium was maintained. Visual success was measured by an improvement in visual acuity (VA) in the eye during follow-up and directly correlated with central clear graft survival. Results The follow-up period was up to 34 months (mean, 20 months; median, 22.4 months). Mean VA, measured in decimal fractions, increased from 0.029 (∼20/400; median, 0.005; first quartile 0.005; third quartile 0.005) before surgery to 0.281 (20/70; median, 0.2; first quartile 0.04; third quartile 0.55) after surgery. Healthy corneal epithelium showing survival of limbal stem cells was observed in 14 eyes (70%) during complete follow-up. Conclusions Penetrating limbo-keratoplasty with conjunctivoplasty, MMC, and AM transplantation is a promising new surgical technique for improving vision and conjunctivalization in patients with severe bilateral LSCD necessitating allogenic transplants. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose To evaluate retention of visual acuity and development of complications after Boston type 1 keratoprosthesis implantation over a longer follow-up period than previously reported. Design Cohort study. Participants Forty eyes of 35 patients who underwent Boston type 1 keratoprosthesis surgery at the University of California, Davis, between 2004 and 2010. Methods Preoperative, intraoperative, and postoperative parameters were collected and analyzed. Main Outcome Measures Best-corrected visual acuity (BCVA) and postoperative complications. Results Preoperative visual acuity ranged from 20/150 to light perception and was ≤20/400 in 38 eyes (95%). Preoperative diagnoses included failed corneal transplants (19 eyes, 47.5%), chemical injury (10 eyes, 25%), and aniridia (5 eyes, 12.5%). Mean follow-up duration was 33.6 months (range, 5–72 months). Of 36 eyes followed for ≥1 year, 32 eyes (89%) achieved postoperative BCVA ≥20/200. Of eyes that achieved BCVA ≥20/200, at last follow-up, 19 of 32 eyes (59%) followed for ≥1 year retained BCVA ≥20/200; 16 of 27 eyes (59%) followed for ≥2 years retained BCVA ≥20/200; 7 of 14 eyes (50%) followed for ≥3 years retained BCVA ≥20/200; and 2 of 7 eyes (29%) followed for ≥4 years retained BCVA ≥20/200. End-stage glaucoma most commonly caused vision loss (7 of 13 eyes, 54%) when BCVA ≥20/200 was not retained (follow-up ≥1 year). Glaucoma was newly diagnosed in 11 eyes (27.5%); progression was noted in 9 eyes (22.5%). Glaucoma drainage device erosion occurred in 9 eyes (22.5%). Retroprosthetic membrane formed in 22 eyes (55%), 5 eyes (12.5%) developed endophthalmitis, 6 eyes (15%) developed corneal melt, 7 eyes (17.5%) underwent keratoprosthesis replacement, and 23 eyes (57.5%) required major surgery to treat postoperative complications. The initial keratoprosthesis was retained in 32 eyes (80%). Conclusions Keratoprosthesis implantation remains a viable option for salvaging vision. A significant number of patients lost vision over the postoperative course. Glaucoma and complications related to glaucoma surgery are significant challenges to maintaining good vision after keratoprosthesis surgery. Our study highlights the need for long-term follow-up and a team approach to management, and points to a more guarded long-term visual prognosis after surgery. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

To study the association between congenital aniridia and dry eyes, and the status of limbal stem cells.Single-center, retrospective, noninterventional, comparative case series.Twenty patients (36 eyes) diagnosed with congenital aniridia.Retrospective review of medical records at the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia to identify all cases of congenital aniridia. Selected patients were requested to undergo further testing, especially for evaluation of dry eyes. Full ocular examinations were performed, including examination of the meibomian gland orifices and dry eye evaluation (by predetermined criteria of tear breakup time, tear meniscus level, presence of mucoid secretions, Schirmer's test with and without anesthesia, and fluorescein and rose Bengal staining patterns of the cornea and conjunctiva). Cytological evaluation was performed in 23 aniridic eyes by impression cytology to determine limbal stem cell status relative to control normal eyes.Abnormal tear film production and stability, meibomian gland dysfunction, severity of corneal involvement, and limbal stem cell deficiency.Twenty patients (36 eyes) diagnosed with congenital aniridia were classified into 3 groups according to the severity of corneal involvement: mild (2 eyes), moderate (21 eyes), and advanced (13 eyes) corneal changes. Tear breakup time was reduced by an average of 5 seconds in 90.7% of cases, tear meniscus levels were reduced to0.5 mm in 88.6% of cases, and stenosed meibomian orifices were found in 77.8% of patients. Dry eyes (94%) correlated with the severity of corneal involvement (P = 0.001). Impression cytology revealed metaplasia in all tested cases. Furthermore, 8 of 23 eyes (35%) and 15 of 23 eyes (65%) had early and advanced limbal stem cell deficiency, respectively.Abnormal tear film stability and meibomian gland dysfunction are newly identified factors in patients with aniridia. Both correlate to the severity of ocular surface disease. Impression cytology is informative in diagnosing various degrees of limbal stem cell deficiency, which is present in all tested aniridia eyes.

Objective Aniridic keratopathy is a major cause of vision loss in patients with aniridia. Penetrating keratoplasty has been proven ineffective for the long-term treatment of this disorder because it does not address the stem cell deficiency that is the primary etiologic factor. We evaluated the role of keratolimbal allograft (KLAL), a stem cell transplantation technique, for the treatment of patients with aniridic keratopathy. Design Retrospective noncomparative interventional case series. Participants Thirty-one eyes of 23 patients with aniridic keratopathy. Intervention KLAL. Main outcome measures Ocular surface stability, visual acuity, and success of subsequent penetrating or lamellar keratoplasty. Results Thirty-one eyes of 23 patients were treated with KLAL and followed up for 12 to 117 months (mean, 35.7 months). Twenty-three eyes (74.2%) achieved a stable ocular surface. Overall, the mean visual acuity improved from 20/1000 to 20/165. Twenty eyes (64.5%) underwent subsequent penetrating keratoplasty. Fourteen corneal transplant grafts (70.0%) were successful, and six (30.0%) failed. Nineteen (90.5%) of 21 eyes receiving systemic immunosuppression obtained a stable ocular surface, whereas only 4 (40.0%) of 10 eyes not receiving systemic immunosuppression achieved ocular surface stability ( P Conclusions KLAL is effective in treating aniridic keratopathy. Patients receiving systemic immunosuppression have a greater likelihood of achieving ocular surface stability and improved visual acuity compared with those who receive only topical immunosuppression.

Objective To investigate the feasibility of handheld (HH) ultra-high-resolution spectral-domain optical coherence tomography (SD-OCT) in young children with nystagmus, to determine its sensitivity and specificity in classifying foveal abnormalities, and to investigate its potential to determine the cause of infantile nystagmus with the use of foveal morphology. Design Prospective, case-control study. Participants and Controls A total of 50 patients with nystagmus and 50 healthy control subjects (mean age, 3.2 years; range, 0–8 years). Methods Each patient was scanned using HH SD-OCT (Bioptigen Inc., Research Triangle Park, NC) without sedation, and foveal morphology was classified into 1 of 4 categories: (1) typical foveal hypoplasia (predicting clinical diagnosis of albinism, PAX6 mutations, or isolated foveal hypoplasia); (2) atypical foveal hypoplasia (predicting achromatopsia); (3) other foveal changes (corresponding to retinal dystrophies); and (4) normal fovea (predicting idiopathic or manifest latent nystagmus). An independent interpretation of the HH SD-OCT scans by masked examiners was performed, and the sensitivity and specificity of the predicted diagnosis were calculated. Main Outcome Measures The success rate of image acquisition and sensitivity and specificity of the HH SD-OCT in classifying foveal abnormalities. Results In 94% of examinations, HH SD-OCT was successful. Twenty-three patients had typical foveal hypoplasia (category 1). Of these patients, 21 were diagnosed with albinism and 2 were diagnosed with PAX6 mutations. Five patients were classified as atypical (category 2) and diagnosed with achromatopsia. Six patients had other abnormal foveal morphology (category 3) and were diagnosed with retinal dystrophy. Sixteen patients had normal foveal morphology (category 4). Of these patients, 12 were diagnosed with idiopathic nystagmus and 4 were diagnosed with manifest latent nystagmus. Sensitivities of HH SD-OCT for classifying typical or atypical foveal hypoplasia, other abnormal foveal morphology, and normal morphology were 92.8%, 86.7%, 41.1%, and 88.4%, respectively, with specificities of 91.4%, 94.8%, 97.7% and 95.1%, respectively. Conclusions We demonstrate excellent feasibility of HH SD-OCT in the diagnosis of conditions associated with infantile nystagmus. The HH SD-OCT classification of foveal abnormalities was highly sensitive and specific. This classification was used to determine the underlying cause of infantile nystagmus. Handheld SD-OCT in early childhood can facilitate focused investigations and earlier diagnosis. This is important in an era when potentially time-sensitive treatment, such as gene therapy, is imminent. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Objective: To document the clinical and morphologic corneal findings in the early stages of congenital aniridic keratopathy in Swedish families. less thanbrgreater than less thanbrgreater thanDesign: Prospective, observational, comparative case series. less thanbrgreater than less thanbrgreater thanParticipants: A total of 16 eyes of 16 subjects with congenital aniridic keratopathy and a clear central cornea, and 6 eyes from 6 healthy controls (unaffected relatives). Nine of the 16 eyes with aniridia came from 5 families with a documented familial history of aniridia. less thanbrgreater than less thanbrgreater thanMethods: Detailed ophthalmic examinations included best spectacle-corrected visual acuity (BSCVA), tear film production, tear break-up time (BUT), corneal touch sensitivity, intraocular pressure measurement, ultrasound pachymetry, slit-lamp biomicroscopy, and laser scanning in vivo confocal microscopy (IVCM). less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Confirmed stage of aniridic keratopathy, clinical parameters of cornea and tear film (visual acuity, sensitivity, corneal thickness, tear production, and BUT), and the morphologic status of corneal epithelium, sub-basal nerves, and limbal palisades of Vogt. less thanbrgreater than less thanbrgreater thanResults: In early-stage aniridic keratopathy, BSCVA and tear BUT were reduced relative to controls (P andlt; 0.001 for both), and corneal thickness was increased (P = 0.01). Inflammatory dendritic cells were present in the central epithelium in aniridia, with significantly increased density relative to controls (P = 0.001). Discrete focal opacities in the basal epithelial region were present in 5 of 11 aniridia cases with an otherwise clear cornea. Opacities were associated with dendritic cells and harbored structures presumed to be goblet cells. Sub-basal nerves were extremely dense in 3 aniridia cases, and a prominent whorl pattern of nerves and epithelial cells was observed in 1 case. Normal limbal palisade morphology was absent in aniridia but present in controls. less thanbrgreater than less thanbrgreater thanConclusions: Early-stage aniridic keratopathy is characterized by the development of focal opacities in the basal epithelium, altered sub-basal nerves, infiltration of the central epithelium by dendritic cells, tear film instability, and increased corneal thickness and degradation of limbal palisade architecture. These findings may help to elucidate the pathogenesis of aniridic keratopathy. less thanbrgreater than less thanbrgreater thanFinancial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Funding Agencies|European Union||Crown Princess Margaretas Foundation for the Visually Impaired||Swedish Eye Fund||Carmen and Bertil Regners Foundation||David and Beth Dahlins Foundation||King Gustav V and Queen Victorias Freemasons Foundation||County Council of Ostergotland||Association of the Blind in Ostergotland

To describe clinical and molecular characteristics of Korean patients with aniridia and to compare the clinical phenotype between those having an identifiable PAX6 mutation and those not.Comparative case series.A total of 14 Korean patients from 10 families with aniridia.Complete ophthalmologic examinations were performed for all patients. PAX6 analysis included direct sequencing of all coding regions and multiplex ligation-dependent probe amplification (MLPA) to detect large deletions when the sequencing was negative. If the PAX6 analysis failed to reveal any identifiable mutations, genomic copy number variation analysis via array comparative genomic hybridization (CGH) and candidate gene PITX3 and FOXE3 sequencing were then performed.Severity of ocular abnormalities and genetic findings.Sequencing of PAX6 exhibited 5 different heterozygous mutations in 8 patients from 5 families; 2 (p.Ser43Phe, IVS8-9CG) were novel, and 3 (p.Arg208Trp, p.Arg317X, and p.X423L) have been previously reported. Among the remaining 6 patients in whom the PAX6 sequencing was negative, MLPA identified large deletions in 2 sporadic patients. However, the array CGH and candidate gene sequencing found no genomic or genetic abnormalities. The mutation detection rate was therefore 70%. Patients harboring an identifiable mutation in PAX6 had either a severe or a mild variant phenotype depending on the type of mutations. Likewise, among patients without an identifiable PAX6 mutation, their phenotypes varied widely from severe to very mild.This study adds 2 novel PAX6 mutations to those previously reported, providing further evidence for genetic and phenotypic heterogeneity in aniridic ocular malformation. There was no difference in the clinical phenotype between patients with and without detectable mutations in the PAX6 gene. The wide variability of ocular phenotype regardless of the presence or absence of PAX6 mutations calls for a further appreciation of the complexity in the molecular diagnosis of aniridia and suggests that this ocular malformation may be better regarded as a group of heterogeneous disorders, rather than a single disease entity, associated with mutations in PAX6 and/or other genes located elsewhere in the human genome.The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Purpose To clinically and molecularly characterize a group of patients with progressive limbal stem cell deficiency (LSCD) due to aniridic keratopathy (AK), but with minimally affected irides. Design Retrospective case series. Participants A total of 12 eyes of 6 patients who underwent keratolimbal allograft (KLAL) for AK in the absence of the classic stigmata of aniridia at the Cincinnati Eye Institute/University of Cincinnati between 2000 and 2007. Methods Retrospective chart review. Main Outcome Measures Ocular surface stability after KLAL and change in visual acuity. Results Subjects' mean age was 32.57 years, 66% were female, and mean follow-up was 64.4 months (range, 20–115 months). All patients presented with a decline in their vision secondary to LSCD. Average preoperative best-corrected visual acuity (BCVA) logarithm of the minimum angle of resolution (logMAR) was 1.4 (range, 0.10–2.8). All patients had minimally affected irides with subtle abnormal findings, including ectropion uveae and stromal atrophy. All patients developed severe LSCD and required KLAL. Average postoperative logMAR BCVA was 0.35 (range, 0.00–1.00). All ocular surfaces remained stable throughout the follow-up period. Family history consistent with autosomal dominant inheritance was positive in 4 of 6 patients. PAX6 genetic testing identified 2 pathologic mutations and 1 possible disease-causing variant. Conclusions Aniridic keratopathy may present in the absence of other classic stigmata of aniridia and be associated with minimally affected irides. A subset of these patients has definitive mutations in PAX6 and once identified can be counseled appropriately. These patients respond well to KLAL and may therefore benefit from early detection. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

OBJECTIVE: To evaluate the biometry accuracy, visual outcomes, and long-term changes in intraocular pressure after implantation of the black diaphragm intraocular (BDI) lens in cases of aniridia. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Forty eyes of 35 patients with aniridia (15 eyes of congenital origin and 25 as a result of trauma). METHODS: Patient demographics, clinical evolution, and treatment were analyzed for each case undergoing implantation with the Morcher 67F BDI lens (Morcher GmBH, Stuttgart, Germany). MAIN OUTCOME MEASURES: Biometry accuracy, visual outcome, and the development of glaucoma and other complications in these eyes over a mean of 3.5 years. RESULTS: Using the recommended A constant of 118.7, the mean biometry prediction error was -0.12+/-0.44 diopters (D), with a mean absolute error of 1.47+/-0.29 D, equivalent to 80% of target eyes being within 2 D of predicted refraction. The prevalence of glaucoma increased from 10 (25%) of 40 eyes before surgery, to 22 (55%) of 40 eyes at 1 year after surgery. The best-corrected visual acuity in logarithm of the minimum angle of resolution (logMAR) units improved significantly in the 25 eyes with traumatic aniridia, from 1.34+/-0.22 to 0.54+/-0.16 (20/400 to 20/70; P

Purpose To evaluate the use of autologous serum (AS)-derived cultivated corneal epithelial transplantation for the treatment of severe ocular surface disease. Design Retrospective noncomparative case series. Participants Nine eyes from 9 patients with total limbal stem cell deficiency were studied. These consisted of 2 eyes with Stevens–Johnson syndrome, 1 with chemical injury, 1 with ocular cicatricial pemphigoid, 1 with Salzmann corneal dystrophy, 1 with aniridia, 1 with graft-versus-host disease, and 2 with idiopathic ocular surface disease. Methods Autologous serum obtained from patients was used for cultivating corneal epithelial cells on an amniotic membrane substrate. These AS-derived corneal epithelial equivalents were compared with those derived from fetal bovine serum (FBS)-supplemented medium. At the time of surgery, complete removal of the corneal pannus and conjunctiva up to 3 mm from the limbus was performed. Allogeneic (7 cases) and autologous (2 cases) AS-derived cultivated corneal epithelial equivalents were transplanted onto the ocular surface. Postoperative follow-up included serial slit-lamp examinations with fluorescein staining, as well as photographic documentation. Main Outcome Measures Ocular surface reconstruction with corneal epithelialization, graft integrity, visual acuity, and postoperative complications. Results The corneal epithelial sheets cultivated in AS- and FBS-supplemented media were morphologically similar, and demonstrated the normal expression of tissue-specific keratins and junctional specialization assembly proteins. After transplantation, complete corneal epithelialization was achieved within 2 to 5 days. All eyes demonstrated an improvement in visual acuity by ≥2 lines. During the follow-up period of 14.6±4.36 months, the corneal surface of all patients remained stable and transparent, without significant complications. Conclusions Transplantation of AS-derived cultivated corneal epithelial equivalents was shown to be a feasible method of treating patients with severe ocular surface disease. The use of AS is of clinical importance in the development of autologous xenobiotic-free bioengineered ocular surface equivalents for clinical transplantation.

Purpose To evaluate the long-term outcome of ocular surface reconstruction, including keratolimbal allograft (KLAL) and amniotic membrane transplantation (AMT) with or without penetrating keratoplasty (PKP), in patients with nonambulatory vision secondary to total limbal stem cell deficiency (LSCD). Design Retrospective, noncomparative interventional case series. Participants Thirty-nine eyes in 31 consecutive patients with total LSCD, as defined by impression cytology, who had a preoperative best-corrected visual acuity of less than 20/200 and a minimum follow-up of 12 months. Patients were divided into three groups: group 1 (16 eyes) with chemical burns, group 2 (9 eyes) with Stevens-Johnson syndrome (SJS), and group 3 (14 eyes) with other causes of LSCD, including ocular cicatricial pemphigoid, atopic keratoconjunctivitis, and aniridia. Intervention All patients underwent KLAL and AMT by one surgeon (SCGT). If needed, PKP was performed at the same surgical setting using tissue from the same donor. Main outcome measures Cumulative rates of survival of ambulatory vision (≥ 20/200), survival of KLAL, survival of PKP, and incidence of complications. Results Fifty-three KLAL with AMT procedures were performed in 39 eyes, of which 23 eyes received simultaneous PKP at the time of the first KLAL. The mean follow-up was 34.0 ± 21.5 months (range, 12–117.6). The mean period of ambulatory vision was 23.9 ± 20.9 months (range, 0–104). The overall survival of ambulatory vision was 53.6% at 3 years and 44.6% at 5 years. The survival of ambulatory vision was significantly worse in SJS compared with other causes (67%, 81%, and 92% for groups 1, 2, and 3, respectively; P = 0.06 for group 1 versus 2, P = 0.0008 for group 1 versus 3). KLAL performed alone resulted in higher survival of ambulatory vision at 2 years (86.1% ± 9.1%) compared with KLAL with PKP (46.9% ± 10.6%, P = 0.100). The survival of PKP was significantly worse in SJS compared with the other causes (20.0% ± 17.9% compared with 55.6% ± 11.7%, respectively, P = 0.028). After 2 years, the survival of the second KLAL was better than that of the first: 68.2% ± 15.4% compared with 27.3% ± 13.4%, respectively ( P = 0.041). Conclusions Ambulatory vision for a period of more than 2 years can be achieved by KLAL with or without PKP in eyes with severe ocular surface disorders caused by total LSCD. However, a progressive decline of the visual outcome and graft survival is evident with time. Performing PKP simultaneously with KLAL may be associated with a less favorable outcome. The failure of KLAL is associated with the loss of donor cells in the recipient. Augmentation of ocular surface defense is essential in securing the success of KLAL and PKP. Future modifications of the surgical procedure and of the immune suppressive protocols may improve survival of the allogeneic grafts and the final visual outcome.

To use molecular genetic techniques to prenatally screen for aniridia.Case report.DNA was extracted from cultured fibroblasts obtained through amniocentesis. Two mutation detection methods, Ava1 restriction digestion and single-strand conformational polymorphism electrophoresis, were used to screen the PAX6 gene.The results from the amniocentesis sample were compared with DNA obtained from the affected father, firstborn infant, and unaffected mother to determine whether the fetus carried the PAX6 mutation.DNA from the fetus demonstrated the same banding pattern as the affected father and firstborn infant.The fetus carried the mutated PAX6 allele and was predicted to develop aniridia. This was later confirmed when the child was born. This case report illustrates an important use of genetic mutation screening in the clinical setting.

Objective: The purpose of this study is to determine the efficacy of initial trabeculotomy in the patient with aniridic glaucoma. Design: Clinical charts were reviewed. Participants: Twenty-nine eyes of 16 patients with aniridia were studied. Intervention: Glaucoma surgery was performed. As an initial procedure, trabeculotomy was performed in 12 eyes, other surgery was performed in 17 eyes (trabeculectomy, 5; goniotomy, 5; other, 7). Main Outcome Measures: Success was defined as an intraocular pressure (lOP) of 21 mmHg or lower, and no further surgery was performed. Results: Ten (83%) of 12 eyes obtained lOP control after first (6 eyes) or second (4 eyes) trabeculotomy with a mean follow-up period of 9.5 years. Five eyes maintained visual acuity of 20/40 to 20/200. No serious complications were found after trabeculotomy. Three (18%) of 17 eyes were controlled with the first glaucoma surgery other than trabeculotomy (goniotomy, trabeculectomy, trabeculectomy combined with trabeculotomy, and Molteno implant). Good lOP control was obtained in 8 (47%) of 17 eyes after several surgeries with a mean follow-up period of 10.4 years. Four of 17 eyes became phthisical. Conclusion: This study suggests that trabeculotomy is the preferred initial operation for uncontrolled glaucoma with aniridia.

The purpose of the study is to determine the safety and efficacy of mitomycin C-augmented trabeculectomy in children with developmental glaucoma treated previously by conventional procedures.Retrospective review of all cases of developmental glaucoma with previously failed conventional procedures that underwent mitomycin C-augmented trabeculectomy between January 1992 and December 1994.A total of 19 eyes of 13 patients were included in the study. Nineteen eyes included primary congenital glaucoma (15 eyes) with documented failure of primary trabeculotomy, Axenfeld-Reiger syndrome (2 eyes) and aniridia (2 eyes).Mitomycin C-augmented (0.4 mg/ml for 3 minutes) trabeculectomy was the chosen intervention.Preoperative and postoperative intraocular pressures (IOPs), visual acuities, success rate, bleb characteristics, time of surgical failure, and complications were the main outcome measures.The mean IOP was reduced from a preoperative level of 33.74 +/- 10.70 mmHg to 11.89 +/- 1.33 mmHg (P0.0001) with the percentage reduction in IOP being 64.75. The mean follow-up was 19.52 +/- 2.65 months. Visual acuity was maintained in all the cases after surgery. Complete success as defined in the authors' study was achieved in 18 eyes (94.74%). Only one patient was classified as a qualified success. The bleb was characterized by its large elevated, avascular, transparent appearance in all the eyes. The only significant complication was retinal detachment in an eye with buphthalmos, aphakia, and large axial length. However, the retina was reattached successfully by retinal reattachment surgery, and visual acuity improved to the preoperative level of 20/200. It was not possible to determine the cause of retinal detachment or to assess the possible role of mitomycin C in this complication.Mitomycin C-augmented trabeculectomy is a viable option in eyes with failed conventional trabeculotomy surgery.

Purpose: To determine which human corneal diseases show similar abnormal corneal surfaces, characterized by conjunctival epithelial ingrowth (conjunctivalization), vascularization, and chronic keratitis (i.e., a constellation of signs termed limbal stem cell dysfunction [deficiency], which have been noted in experimental rabbit models). Methods: A total of 134 impression cytology specimens of the perilimbal region collected from 1984 to 1994 were reviewed. Limbal deficiency was diagnosed if conjunctival goblet cells were found on the corneal surface. Results: Ninety-four patients were found to have limbal deficiency. Category 1 comprised 53 patients with a clear history showing limbal stem cell destruction by chemical/thermal burns, Stevens-Johnson syndrome, multiple surgeries and cryotherapies, contact lens wear, and severe microbial keratitis. Patients in category 2 (n = 41), did not have such a history, but gradual loss of stem cell functions overtime was disclosed and included diverse causes such as aniridia, multiple endocrine deficiencies, neurotrophic keratopathy, peripheral inflammatory keratopathy or limbitis, and idiopathy. The 40 remaining patients with suspicious findings did not have limbal deficiency. Conclusions: Impression cytology can be used to diagnose and monitor corneal diseases with limbal deficiency, which manifest distinct clinical problems and are generally poor candidates for penetrating keratoplasty. The identification of category 1 diseases allows one to consider limbal (stem cell) transplantation for surface reconstruction. The presence of category 2 diseases indicates that limbal stem cell functions can be modulated by developmental, hormonal, neuronal, vascular, and inflammatory factors in the limbal stroma.

Visual rehabilitation of patients with aniridia and progressive cataract is a challenging clinical problem. Reduced corneal transparency, limitations of iris support, and decreased zonular integrity may make extracapsular cataract surgery difficult. Four patients with familial aniridia had substantial visual improvement after successful extracapsular cataract extraction (ECCE) with implantation of capsular-fixated posterior chamber intraocular lenses (PC IOLs). In one patient, it was combined with trabeculectomy to treat chronic open-angle glaucoma. Posterior chamber IOLs can be safely implanted in the aniridic eye normalities in the anterior segment.

We recently studied members from a family with autosomal dominant iris coloboma. All affected members had either unilateral or bilateral iris coloboma and bilateral peripheral corneal changes indistinguishable from those seen in aniridia. The corneal changes consisted of well-demarcated pannus-like growths extending from the limbus onto the peripheral cornea for 360° without any stromal vascularization. In one adolescent member, bilateral lenticular opacities limited to the meridian of the colobomata were seen. No members had primary glaucoma, macular or optic disc hypoplasia, nystagmus, or extraocular malformations. The coexistence of iris coloboma and aniridia-like corneal changes may imply that ocular coloboma and aniridia comprise a continuous spectrum of the same developmental defect or, alternatively, such corneal changes constitute a nonspecific manifestation of iris developmental defects in general.

A child with aniridia, multiple anomalies, severe failure to thrive, and severe psychomotor retardation is shown to have a syndrome similar to, though more severe than, other patients with overlapping deletions of the short arm of chromosome 11 (Pediatrics 64:604, 1978). Her deletion (46,XX,del [11p] [pter yields p14::p11.3 yields qter]) was derived from her mother, who has a chromosome 11 shift (46,XX,der [11] [pter yields p14::p11.3 yields q22::p14 yields p11.3::q22 yields qter]). The significance of del (11p) in the aniridia-Wilms' tumor association is discussed, and the del (11p) basis for aniridia is compared with other genetic bases for aniridia.

Thirty-eight eyes were treated by adding timolol to the medical regimen. After a suitable trial, attempts were made to reduce other glaucoma medications. Fifteen eyes with infantile glaucoma treated surgically at birth, experienced elevated intraocular pressure later in life. Another 15 eyes had glaucoma associated with congenital anomalies such as aniridia, Sturge-Weber syndrome, and mesodermal malformation. The group with infantile glaucoma demonstrated an average drop in pressure of 24% and 22% after one and three months, respectively. Six of the 15 eyes were controlled at 22 mm Hg or less. In the other group, intraocular pressure fell 30% after one month and 12% after three months. Five of the 15 eyes were controlled. Adverse effects occurred in five patients, timolol therapy was discontinued in two (7%). The IOP was not controlled in any of the eyes with timolol alone.